Oral ulcerative lesions are an important cause of morbidity among HIV- infected individuals, often causing serious difficulties in complying with therapeutic regimens and sufficient nutrient and fluid intake. Some of these ulcers represent aphthous stomatitis which usually responds well to corticosteroid treatment, while data from a number of laboratories suggest that human cytomegalovirus (HCMV), and possibly herpes simplex virus (HSV), are involved in the pathogenesis of other persistent oral ulcerations. In addition, necrotizing stomatitis, gingivitis and periodontitis are ulcerative lesions that not only have a bacterial component but also may demonstrate concurrent infection with HCMV and HSV. Unfortunately, the reports of these persistent oral ulcers, published to date, have involved relatively small numbers of patients. The research proposed in this project will attempt to determine the role of HCMV and other factors (e.g., HSV) in the development and progression of persistent oral ulcers. Sections from surgical specimens of chronic oral ulcerations which have not responded to empirical drug therapy will be examined for virus-induced cytopathic changes and the presence of virus-specific components by immunohistochemical methods, in situ hybridization, and the multiplex polymerase chain reaction (PCR) to identify the specific cell types and virus(es) that are involved in these lesions. Saliva from individuals afflicted with persistent oral lesions and from those without these lesions will be monitored for human herpesviruses by culture and by quantitative PCR. Individuals with demonstrated involvement of HCMV in their persistent oral ulcers will be treated with ganciclovir to evaluate the potential of this therapeutic approach to manage these lesions. The contribution of several mechanisms of cellular injury associated with HCMV infection to the development and progression of persistent oral ulcers will be examined in an effort to begin to better characterize the pathogenesis of these lesions.